Primecuts – This Week in the Journals

October 9, 2020

By Sunny Kim, MD

Peer reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose. 

Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study [1]

Treatment of type 2 diabetes is highly dynamic, especially in the use of second or third-line treatments. The use of sodium glucose co-transporter 2 (SGLT2) inhibitors have been shown to be beneficial for patients in multiple randomized control trial studies compared to placebos, showing benefits in areas such as decreased hospitalization stay and cardiovascular death [2-3].

This multi-database retrospective cohort study used a prevalent new user design to population-based data, to compare the risks and benefits of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors, both of which are popular second or third line anti-diabetic therapies. This study is different from previous studies in that previous studies only compared SGLT2 inhibitors to placebos while excluding comparator drugs, while this study is directly comparing SGLT2 inhibitors to DPP-4 inhibitors. As both are popular second or third line anti-diabetic therapies, this comparison has important clinical implications.

The authors analyzed 209,869 matched pairs of new SGLT2 inhibitor users with DPP-4 users. SGLT2 inhibitors were associated with statistically significant decreased risk of MACE compared to DPP-4 inhibitors (hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), as well as decreased risk of myocardial infarction (0.82, 0.70 to 0.96), cardiovascular death (0.60, 0.54 to 0.67), all-cause mortality (0.60, 0.54 to 0.67), and hospital admission for heart failure (0.43, 0.37 to 0.51). In addition, while modest, SGLT2 inhibitors were also associated with decreased risk of ischemic stroke (0.85, 0.72 to 1.01). The authors concluded that more SGLT2 inhibitors may offer short term cardioprotective benefits over DPP-4 inhibitors, but additional studies are needed to determine long-term benefits.

Short or Long Sleep Duration and CKD: A Mendelian Randomization Study [4]

While sleep duration and behaviors have been known to be associated with kidney function and cardiovascular disease risk in multiple studies, the relationship between the exact duration, short versus long, and risk of chronic kidney disease (CKD) is unclear [5-8].

In this observational cohort study, the authors analyzed the self-reported sleep duration by 465,814 patients in UK Biobank prospective cohort. The UK Biobank was constructed prospectively by contacting participants aged 40-69 from 2006 to 2010 in the United Kingdom for participation in clinical interview, anthropometric evaluations, and laboratory measurements. Sleep duration was categorized by short (<6 hours in 24 hours), intermediate (6-8 hours), and long (>9 hours). The authors used Mendelian randomization for analysis, which is a method that can demonstrate a causal effect of modifiable environmental factors on complex disease phenotypes, as highlighted in this study [9].

Both short and long sleep durations were clinically associated with higher prevalence of CKD stages 3 to 5, compared to intermediate sleep durations. However, only the short sleep duration was statistically significantly related to CKD stages 3-5 (adjusted odds ratio, 1.80; 95% confidence interval, 1.25 to 2.60; P=0.002). The authors recommend counseling patients to avoid short-duration sleep to reduce the risk of CKD, especially in vulnerable populations.

HPV Vaccination and the Risk of Invasive Cervical Cancer [10]

While the effect of quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown to be significant at a population level, its effect on subsequent invasive cervical cancer is unclear.

This prospective observational study used the Swedish demographic and health registers to follow 1,672,983 women between ages 10 and 30 from 2006 to 2017 to track the association between HPV vaccination and invasive cervical cancer. The study found a statistically significant increased incidence of cervical cancer in unvaccinated women versus vaccinated women with incidence rate ratio of 0.51 (95% confidence interval [CI], 0.32 to 0.82). Those who had initiated vaccination before 17 years of age had the lowest incidence of cervical cancer (4 cases per 100,000), with cumulative incidence among vaccinated women being lower than unvaccinated women (47 vs 94 cases per 100,000).

In conclusion, as expected, HPV vaccination is associated with reduced risk of invasive cervical cancer at the population level, as well as prevention of high-grade cervical lesions.


Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging for Detection of Coronary Artery Disease [11]

The use of gadobutrol as contrast in detection of coronary artery disease by use of cardiovascular magnetic resonance (CMR) imaging has not been approved in the United States yet. CMR imaging with late gadolinium enhancement was shown to have high diagnostic accuracy in phase 2 and 3 clinical trials, with optimal detection threshold at 63-67% stenosis.

In-hospital Cardiac Arrest in Critically Ill Patients with CoVID-19: Multicenter Cohort Study [12]

Since the beginning of the CoVID-19 pandemic, the poor outcome of critically ill older patients with cardiac arrest, even with timely cardiopulmonary resuscitation, has been anecdotally reported. However, a multi-center cohort study of geographically diverse intensive care units showed that overall survival rate after CPR was similar to non-CoVID-19 related critical illness, at 12 percent of patients who received CPR surviving to discharge.

Evidence for Exacerbation-Prone Asthma and Predictive Biomarkers of Exacerbation Frequency [13]

The successful treatment of exacerbation-prone asthma lies in prevention and prediction of said exacerbations. This study showed that blood measures of IL-6, but not eosinophils, correlate with increased incidence of exacerbation by 10 percent for each 1 pg/uL increase in baseline IL-6 level.

Dr. Sunny Kim is a 1st year resident at NYU Langone Health

Peer reviewed by Roisin Finan, MD, associate editor, Clinical Correlations

Image courtesy of Wikimedia Commons


[1] Filion KB, Lix LM, Yu OH, et al. Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study. BMJ 2020; 370:m3342.

[2] Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8; 383(15):1413-1424.

[3] Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 Jan 24; 380(4):347-357.

[4] Park S, Lee S, Kim Y, et al. Short or Long Sleep Duration and CKD: A Mendelian Randomization Study. JASN October 2020, ASN.2020050666.

[5] McMullan CJ, Curhan GC, Forman JP. Association of short sleep duration and rapid decline in renal function. Kidney Int 89: 1324–1330, 2016.

[6] Ricardo AC, Knutson K, Chen J, et al. Chronic Renal Insufficiency Cohort (CRIC) Study Investigators: The association of sleep duration and quality with CKD progression. J Am Soc Nephrol 28: 3708–3715, 2017.

[7] Yamamoto R, Shinzawa M, Isaka Y, et al. CKD-JAC Investigators: Sleep quality and sleep duration with CKD are associated with progression to ESKD. Clin J Am Soc Nephrol 13: 1825–1832, 2018.

[8] Daghlas I, Dashti HS, Lane J, et al. Sleep duration and myocardial infarction. J Am Coll Cardiol 74: 1304–1314, 2019.

[9] Davies NM, Holmes MV, Davey Smith G. Reading mendelian randomization studies: A guide, glossary, and checklist for clinicians. BMJ 362: k601, 2018.

[10] Lei J, Ploner A, Elfstrom KM, et al. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med 2020; 383:1340-1348.

[11] Arai AE, Schulz-Menger J, Berman D, et al. Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging for Detection of Coronary Artery Disease. JACC September 2020; 76(13).

[12] Hayek SS, Brenner SK, Azam TU, et al. In-hospital cardiac arrest in critically ill patients with covid-19: multicenter cohort study. BMJ 2020; 371.

[13] Peters MC, Mauger D, Ross KR, et al. Evidence for Exacerbation-Prone Asthma and Predictive Biomarkers of Exacerbation Frequency. Am J Respir Crit Care Med. 2020